a safety and efficacy study of shr3680 in metastatic castration-resistant prostate cancer patients

Conditions: Hormone Refractory Prostate Cancer; Metastatic Prostate Carcinoma

Summary: this study evaluates the tolerability, safety, pharmacokinetics and efficacy of shr3680 in patients with metastatic castration-resistant prostate cancer (mcprc). all participants will receive shr3680.

androgenic signaling plays a pivotal role in the development of prostate cancer. androgen deprivation therapy is the mainstay treatment for this cancer in the metastatic setting, but the disease eventually develops to castration-resistant prostate cancer (crpc) mainly due to the overexpression of androgen receptors (ar) and continued ar activation. shr3680 is a novel strong ar antagonist. by competitively binding to ar, shr3680 inhibits androgen-mediated translocation of ar to the nucleus, binding of ar to deoxyribonucleic acid (dna), and finally the transcription of ar target genes, thus possibly resulting in a specific and strong anti-tumor effect on prostate cancer. unlike first-generation ar antagonists (e.g. bicalutamide), which undergoes an antagonist-to-agonist switch to stimulate ar in the setting of ar overexpression in crpc, shr3680 is a full antagonist of ar and thus it is supposed to be more effective for the treatment of crpc.

Eligibility criteria:
inclusion criteria: * ecog performance scale 0 - 1. * life expectancy of more than 6 months. * histologically or cytologic confirmed prostate adenocarcinoma without neuroendocrine differentiation or small cell features * ongoing androgen deprivation therapy with a gonadotropin releasing hormone (gnrh) analogue or orchiectomy * evidence of prostate cancer progression by radiographic or psa criteria * radiological evidence of distant metastatic lesions * serum testosterone level \< 1.7 nmol/l (50 ng/dl) at the screening visit * adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 10e9/l, neutrophil \> 1.5 × 10e9/l, hb \>90 g/l,total bilirubin and creatinine within upper limit of normal(uln), and serum transaminase≤1.5×the uln). * signed and dated informed consent.willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. exclusion criteria: * treatment with androgen receptor antagonists, 5-alpha reductase inhibitors, estrogens, or chemotherapy within 4 weeks of enrollment or plans to initiate treatment with any of these drugs during the study * prior treatment with enzalutamide, abiraterone, or ketoconazole for prostate cancer * history of seizure or any conditions that may predispose to seizure * concurrent or planned treatment with corticosteroids, medications known to have seizure potential, or herbal products known to decrease psa levels * planned to initiate any other anti-tumor therapies during the study * less than 4 weeks from the last clinical trial * evidence of brain metastasis or primary tumors * clinically significant cardiovascular diseases * abuse of alcohol or drugs * severe concurrent disease, infection, or bone metastasis that, in the judgment of the investigator, would make the patient inappropriate for enrollment